Sample processing devices and carriers

ABSTRACT

Methods and devices for thermal processing of multiple samples at the same time are disclosed. The assemblies include carriers and sample processing devices with process arrays that include conduits useful in distributing sample materials to a group pf process chambers located in fluid communication with the main conduits. The sample processing devices may include one or more of the following features in various combinations: deformable seals, process chambers connected to the main conduit by feeder conduits exiting the main conduit at offset locations, U-shaped loading chambers, and a combination of melt bonded and adhesively bonded areas. The carriers may be used to apply selective compression to the sample processing devices.

RELATED APPLICATIONS

This application is a continuation of 10/929,044, filed Aug. 27, 2004which is a divisional application of U.S. Ser. No. 09/895,001, filedJun. 28, 2001, now U.S. Pat. No. 6,814,935, which is acontinuation-in-part of U.S. patent application Ser. No. 09/710,184,filed Nov. 10, 2000, now U.S. Pat. No. 6,627,159 and claims the benefitof U.S. Provisional Patent Application Ser. No. 60/214,508 filed on Jun.28, 2000.

GRANT INFORMATION

The present invention may have been made with support from the U.S.Government under NIST Grant No. 70NANB8H4002. The U.S. Government mayhave certain rights in the inventions recited herein.

FIELD OF THE INVENTION

The present invention relates to the field of sample processing devices.More particularly, the present invention relates to assemblies of sampleprocessing devices and carriers, as well as methods of using the sampleprocessing devices.

BACKGROUND

Many different chemical, biochemical, and other reactions are sensitiveto temperature variations. The reactions may be enhanced or inhibitedbased on the temperatures of the materials involved. In many suchreactions, a temperature variation of even 1 or 2 degrees Celsius mayhave a significantly adverse impact on the reaction. Although it may bepossible to process samples individually and obtain accuratesample-to-sample results, individual processing can be time-consumingand expensive.

One approach to reducing the time and cost of processing multiplesamples is to use a device including multiple chambers in whichdifferent portions of one sample or different samples can be processedsimultaneously. However, this approach presents several temperaturecontrol related issues. When using multiple chambers, the temperatureuniformity from chamber to chamber may be difficult to control. Anotherproblem involves the speed or rate at which temperature transitionsoccur when thermal processing, such as when thermal cycling. Stillanother problem is the overall length of time required to thermal cyclea sample(s).

The multiple chamber device may include a distribution system. However,the distribution system presents the potential for cross-contamination.Sample may inadvertently flow among the chambers during processing,thereby potentially adversely impacting the reaction(s) occurring in thechambers. This may be particularly significant when multiple samples arebeing processed. In addition, the distribution system may presentproblems when smaller than usual samples are available, because thedistribution system is in fluid communication with all of the processchambers. As a result, it is typically not possible to prevent deliveryof sample materials to all of the process chambers to adapt to thesmaller volume samples.

Thermal processing, in and of itself, presents an issue in that thematerials used in the devices may need to be robust enough to withstandrepeated temperature cycles during, e.g., thermal cycling processes suchas PCR. The robustness of the devices may be more important when thedevice uses a sealed or closed system.

SUMMARY OF THE INVENTION

The present invention provides methods and devices for thermalprocessing of multiple samples at the same time. The sample processingdevices provide process arrays that include conduits useful indistributing sample materials to a group of process chambers located influid communication with the main conduits. The sample processingdevices may include one or more of the following features in variouscombinations: deformable seals, process chambers connected to the mainconduit by feeder conduits exiting the main conduit at offset locations,U-shaped loading chambers, and a combination of melt bonded andadhesively bonded areas.

If present in the sample processing devices of the present invention,deformable seals may provide for closure of the main conduits to preventleakage. Deformable seals may also provide for isolation of the processchambers located along the main conduit, such that cross-contamination(e.g., migration of reagent between process chambers after introductionof sample material) between the process chambers may be reduced oreliminated, particularly during sample processing, e.g. thermal cycling.Deformable seals may also provide the opportunity to tailor the devicesfor specific test protocols by closing the distribution channels leadingto selected process chambers before distributing sample materials.Alternatively, some deformable seals may be closed to adjust for smallersample material volumes reducing the number of process chambers to whichthe sample materials are distributed.

Sample processing devices of the present invention that include feederconduits connecting the process chambers to the main conduits maypreferably do so using feeder conduits that exit the main conduit atdifferent locations along the main conduit, such that no mainconduit/feeder conduit junctions are directly aligned across the mainconduit. Such an arrangement may provide further reductions in thepossibility of cross-contamination between process chambers by providinga longer path length between the process chambers.

Loading structures in the form of U-shaped loading chambers, whereprovided, may provide advantages in filling of the loading chambers byproviding a structure from which air (or any other fluid located in theloading chamber) can escape during filling.

Sample processing devices that include both melt bonded and adhesivebonded areas may provide the advantage of capitalizing on the propertiesof both attachment methods in a single device. For example, it may bepreferred to use melt bonding in the areas occupied by the processchambers to take advantage of the strength of the melt bonds. In thesame device, it may be possible to take advantage of the sealingproperties of the adhesive bonded areas.

In other aspects, the sample processing devices of the present inventionmay be used in connection with carriers that may, in variousembodiments, provide for selective compression of sample processingdevices, either compression of discrete areas proximate the processchambers or compression of the sample processing devices in the areasoutside of the process chambers. In various embodiments, the carriersmay preferably provide for limited contact between themselves and thesample processing devices, limited contact between themselves and anycompression structure used to compress the carrier and sample processingdevice assembly, and limited thermal mass. The carriers may also provideopenings to allow visual access to the process chambers.

It is also preferred that the sample processing devices of the inventionexhibit robustness in response to the rapid thermal changes that can beinduced due to the relatively high thermal conductivity and relativelylow thermal mass of the devices. This robustness may be particularlyvaluable when the devices are used in thermal cycling methods such as,e.g., PCR. In all thermal processing methods, the preferred devicesmaintain process chamber integrity despite the pressure changesassociated with the temperature variations and despite the differencesbetween thermal expansion rates of the various materials used in thedevices.

Yet another advantage of the present invention is that the devices maybe mass manufactured in a web-based manufacturing process in which thevarious components may be continuously formed and/or bonded, with theindividual devices being separated from the continuous web.

As used in connection with the present invention, the following termsshall have the meanings set forth below.

“Deformable seal” (and variations thereof) means a seal that ispermanently deformable under mechanical pressure (with or without atool) to occlude a conduit along which the deformable seal is located.

“Thermal processing”(and variations thereof) means controlling (e.g.,maintaining, raising, or lowering) the temperature of sample materialsto obtain desired reactions. As one form of thermal processing, “thermalcycling”(and variations thereof) means sequentially changing thetemperature of sample materials between two or more temperaturesetpoints to obtain desired reactions. Thermal cycling may involve,e.g., cycling between lower and upper temperatures, cycling betweenlower, upper, and at least one intermediate temperature, etc.

In one aspect, the present invention provides a sample processingassembly including a sample processing device and a carrier attached tothe sample processing device. The sample processing device includes abody with a first side attached to a second side and a plurality ofprocess arrays formed between the first and second sides. Each processarray of the plurality of process arrays includes a loading structure, amain conduit with a length, a plurality of process chambers distributedalong the main conduit, and a deformable seal located between theloading structure and the plurality of process chambers, wherein themain conduit is in fluid communication with the loading structure andthe plurality of process chambers. The carrier includes a first surfacefacing the sample processing device and a second surface facing awayfrom the sample processing device; a plurality of main conduit supportrails proximate the first surface of the carrier, wherein each mainconduit of the plurality of process arrays is aligned with one mainconduit support rail of the plurality of main conduit support rails; anda plurality of openings formed through the first and second surfaces ofthe carrier, wherein each opening of the plurality of openings isaligned with one process chamber of the plurality of process chambers.

In another aspect, the present invention provides a method of processingsample materials, the method including providing a sample processingassembly that includes a sample processing device attached to a carrier.The sample processing device includes a body with a first side attachedto a second side and a plurality of process arrays formed between thefirst and second sides. Each process array of the plurality of processarrays includes a loading structure, a main conduit with a length, and aplurality of process chambers distributed along the main conduit,wherein the main conduit is in fluid communication with the loadingstructure and the plurality of process chambers. Each of the processarrays also includes a deformable seal located between the loadingstructure and the plurality of process chambers in each process array ofthe plurality of process arrays. The carrier includes a first surfacefacing the sample processing device and a second surface facing awayfrom the sample processing device; a plurality of main conduit supportrails proximate the first surface of the carrier, wherein each mainconduit of the plurality of process arrays is aligned with one mainconduit support rail of the plurality of main conduit support rails; anda plurality of openings formed through the first and second surfaces ofthe carrier, wherein each opening of the plurality of openings isaligned with one process chamber of the plurality of process chambers.The method further includes distributing sample material to at leastsome of the process chambers in each process array of the plurality ofprocess arrays through the main conduit in each of the process arrays;closing the deformable seal in each process array of the plurality ofprocess arrays, the closing including supporting the main conduit withone of the main conduit support rails while compressing the first sideand the second side of the sample processing device together along themain conduit; locating the second side of the sample processing devicein contact with a thermal block; and controlling the temperature of thethermal block while the sample processing device is in contact with thethermal block.

In another aspect, the present invention provides a method of processingsample materials by providing a sample processing assembly including asample processing device attached to a carrier. The sample processingdevice includes a body with a first side attached to a second side and aplurality of process arrays formed between the first and second sides.Each process array of the plurality of process arrays includes a loadingstructure, a main conduit with a length, and a plurality of processchambers distributed along the main conduit, wherein the main conduit isin fluid communication with the loading structure and the plurality ofprocess chambers. The carrier includes a first surface facing the sampleprocessing device and a second surface facing away from the sampleprocessing device; and a plurality of openings formed through the firstand second surfaces of the carrier, wherein each opening of theplurality of openings is aligned with one process chamber of theplurality of process chambers. The method further includes distributingsample material to at least some of the process chambers in each processarray of the plurality of process arrays through the main conduit ineach of the process arrays; locating the second side of the sampleprocessing device in contact with a thermal block; selectivelycompressing the first side and second side of the sample processingdevice together proximate each process chamber of the plurality ofprocess chambers, the selective compression occurring between thecarrier and the thermal block; and controlling the temperature of thethermal block while the sample processing device is in contact with thethermal block.

In another aspect, the present invention provides a sample processingassembly including a sample processing device attached to a carrier. Thesample processing device includes a body with a first side attached to asecond side and a plurality of process arrays formed between the firstand second sides. Each process array of the plurality of process arraysincludes a loading structure, a main conduit with a length, and aplurality of process chambers distributed along the main conduit,wherein the main conduit is in fluid communication with the loadingstructure and the plurality of process chambers. The carrier includes afirst surface facing the sample processing device and a second surfacefacing away from the sample processing device; a plurality of openingsformed through the first and second surfaces of the carrier, whereineach opening of the plurality of openings is aligned with one processchamber of the plurality of process chambers; and a plurality ofcompression structures proximate the first surface of the carrier, eachcompression structure of the plurality of compression structuresproximate one process chamber of the plurality of process chambers.

In another aspect the present invention provides a sample processingassembly that includes a sample processing device attached to a carrier.The sample processing device includes a body with a first side attachedto a second side and a plurality of process arrays formed between thefirst and second sides. Each process array of the plurality of processarrays includes a loading structure, a main conduit with a length, and aplurality of process chambers distributed along the main conduit,wherein the main conduit is in fluid communication with the loadingstructure and the plurality of process chambers. Each process array alsoincludes a deformable seal located between the loading structure and theplurality of process chambers in each process array of the plurality ofprocess arrays. The carrier includes a first surface facing the sampleprocessing device and a second surface facing away from the sampleprocessing device; a plurality of main conduit support rails proximatethe first surface of the carrier, wherein each main conduit of theplurality of process arrays is aligned with one main conduit supportrail of the plurality of main conduit support rails; a plurality ofopenings formed through the first and second surfaces of the carrier,wherein each opening of the plurality of openings is aligned with oneprocess chamber of the plurality of process chambers; and a plurality ofcompression structures proximate the first surface of the carrier, eachcompression structure of the plurality of compression structuresproximate one process chamber of the plurality of process chambers.

In another aspect, the present invention provides a method of processingsample materials, the method including providing a sample processingassembly including a sample processing device attached to a carrier. Thesample processing device includes a body with a first side attached to asecond side and a plurality of process arrays formed between the firstand second sides. Each process array of the plurality of process arraysincludes a loading structure, a main conduit with a length, and aplurality of process chambers distributed along the main conduit,wherein the main conduit is in fluid communication with the loadingstructure and the plurality of process chambers. Each process array alsoincludes a deformable seal located between the loading structure and theplurality of process chambers in each process array of the plurality ofprocess arrays. The carrier includes a first surface facing the sampleprocessing device and a second surface facing away from the sampleprocessing device; a plurality of main conduit support rails proximatethe first surface of the carrier, wherein each main conduit of theplurality of process arrays is aligned with one main conduit supportrail of the plurality of main conduit support rails; and a plurality ofopenings formed through the first and second surfaces of the carrier,wherein each opening of the plurality of openings is aligned with oneprocess chamber of the plurality of process chambers. The method furtherincludes distributing sample material to at least some of the processchambers in each process array of the plurality of process arraysthrough the main conduit in each of the process arrays; closing thedeformable seal in each process array of the plurality of processarrays, the closing including supporting the main conduit with one ofthe main conduit support rails while compressing the first side and thesecond side of the sample processing device together along at least aportion of the length of the main conduit; locating the second side ofthe sample processing device in contact with a thermal block;selectively compressing the first side and second side of the sampleprocessing device together proximate each process chamber of theplurality of process chambers, the selective compression occurringbetween the carrier and the thermal block; and controlling thetemperature of the thermal block while the sample processing device isin contact with the thermal block.

In another aspect, the present invention provides a method of processingsample materials, the method including providing a sample processingassembly including a sample processing device attached to a carrier. Thesample processing device includes a body with a first side attached to asecond side and a plurality of process arrays formed between the firstand second sides. Each process array of the plurality of process arraysincludes a loading structure, a main conduit with a length, and aplurality of process chambers distributed along the main conduit,wherein the main conduit is in fluid communication with the loadingstructure and the plurality of process chambers. Each of the processarrays also includes a deformable seal located between the loadingstructure and the plurality of process chambers in each process array ofthe plurality of process arrays. The carrier includes a first surfacefacing the sample processing device and a second surface facing awayfrom the sample processing device; a plurality of main conduit supportrails proximate the first surface of the carrier, wherein each mainconduit of the plurality of process arrays is aligned with one mainconduit support rail of the plurality of main conduit support rails; anda plurality of openings formed through the first and second surfaces ofthe carrier, wherein each opening of the plurality of openings isaligned with one process chamber of the plurality of process chambers.The method further includes distributing sample material to at leastsome of the process chambers in each process array of the plurality ofprocess arrays through the main conduit in each of the process arrays;closing the deformable seal in each process array of the plurality ofprocess arrays, the closing including supporting the main conduit withone of the main conduit support rails while compressing the first sideand the second side of the sample processing device together along atleast a portion of a length of the main conduit; separating the loadingstructure of each process array of the plurality of process arrays fromthe sample processing device; locating the second side of the sampleprocessing device in contact with a thermal block; and controlling thetemperature of the thermal block while the sample processing device isin contact with the thermal block.

In another aspect, the present invention provides a method of processingsample materials, the method including providing a sample processingassembly including a sample processing device attached to a carrier. Thesample processing device includes a body with a first side attached to asecond side and a plurality of process arrays formed between the firstand second sides. Each process array of the plurality of process arraysincludes a loading chamber, a main conduit with a length, and aplurality of process chambers distributed along the main conduit,wherein the main conduit is in fluid communication with the loadingchamber and the plurality of process chambers. Each of the processarrays also includes a deformable seal located between the loadingchamber and the plurality of process chambers in each process array ofthe plurality of process arrays. The carrier includes a first surfacefacing the sample processing device and a second surface facing awayfrom the sample processing device; a plurality of main conduit supportrails proximate the first surface of the carrier, wherein each mainconduit of the plurality of process arrays is aligned with one mainconduit support rail of the plurality of main conduit support rails; anda plurality of openings formed through the first and second surfaces ofthe carrier, wherein each opening of the plurality of openings isaligned with one process chamber of the plurality of process chambers.The method further includes distributing sample material to at leastsome of the process chambers in each process array of the plurality ofprocess arrays through the main conduit in each of the process arrays;closing the deformable seal in each process array of the plurality ofprocess arrays, the closing including supporting the main conduit withone of the main conduit support rails while compressing the first sideand the second side of the sample processing device together along atleast a portion of the length of the main conduit; separating theloading chambers of each process array of the plurality of processarrays from the sample processing device; selectively compressing thefirst side and second side of the sample processing device togetherproximate each process chamber of the plurality of process chambers, theselective compression occurring between the carrier and the thermalblock; locating the second side of the sample processing device incontact with a thermal block; and controlling the temperature of thethermal block while the sample processing device is in contact with thethermal block.

In another aspect, the present invention provides an apparatus forclosing deformable seals in a sample processing device that includes aplurality of process arrays formed between the first and second sides,wherein each process array of the plurality of process arrays includes aloading structure, a main conduit with a length, and a plurality ofprocess chambers distributed along the main conduit, wherein the mainconduit is in fluid communication with the loading structure and theplurality of process chambers, and further wherein each of thedeformable seals is located between the loading structure and theplurality of process chambers in one process array of the plurality ofprocess arrays. The apparatus includes a base with a cavity adapted toreceive the sample processing device; a bridge operatively attached tothe base, wherein the bridge is capable of traversing a sampleprocessing device received in the cavity along a first direction; and aplurality of sealing structures mounted to the bridge, each of thesealing structures adapted to deform a portion of the sample processingdevice to close one of the deformable seals, wherein the plurality ofsealing structures are aligned along the first direction such that eachmain conduit is sequentially deformed by the plurality of sealingstructures.

In another aspect, the present invention provides a sample processingsystem including a sample processing device that includes a body with afirst side attached to a second side and a plurality of process arraysformed between the first and second sides. Each process array of theplurality of process arrays includes a loading structure, a main conduitwith a length, and a plurality of process chambers distributed along themain conduit, wherein the main conduit is in fluid communication withthe loading structure and the plurality of process chambers. The systemfurther includes a thermal block on which the sample processing deviceis located; and means for simultaneously and selectively compressing thefirst side and second side of the sample processing device together in adiscrete area proximate each process chamber of the plurality of processchambers after locating the second side of the sample processing devicein contact with a thermal block.

These and other features and advantages of the present invention aredescribed below in connection with various illustrative embodiments ofthe devices and methods of the present invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a plan view of one sample processing device of the invention.

FIG. 2 is an enlarged view of a portion of one process array on thesample processing device of FIG. 1.

FIGS. 2A & 2B depict alternative loading chambers for use in sampleprocessing devices of the invention.

FIGS. 3A-3D depict alternative arrangements of process chambers, feederconduits and a main conduit for use in connection with the presentinvention.

FIG. 4 is a cross-sectional view of the portion of the sample processingdevice of FIG. 2, taken along line 4-4 in FIG. 2.

FIG. 5 is a cross-sectional view of FIG. 4, taken along FIG. 5-5 in FIG.4.

FIG. 6 is a cross-sectional view of the main conduit of FIG. 4, takenafter deformation of the main conduit to isolate the process chambers.

FIG. 7 depicts an alternative sample processing device of the presentinvention.

FIG. 8 is an enlarged partial cross-sectional view of the sampleprocessing device of FIG. 7, taken along line 8-8 in FIG. 7.

FIG. 9 depicts an alternative sample processing device of the presentinvention.

FIG. 10 is a cross-sectional view of the sample processing device ofFIG. 9, taken along line 10-10 in FIG. 9.

FIG. 11 depicts an alternative sample processing device of the presentinvention.

FIG. 12 is a perspective view of a sample processing device in which theloading chambers are being separated from the remainder of the sampleprocessing device.

FIG. 13 is a perspective view of the sample processing device of FIG. 12after sealing.

FIG. 14 is a plan view of another sample processing device.

FIG. 15 is a side view of the sample processing device of FIG. 14 afterfolding the device along a line separating the loading chambers from theprocess chambers.

FIG. 16 is an exploded perspective view of an assembly including asample processing device and a carrier.

FIG. 17 is a perspective view of the assembly of FIG. 16 as assembled.

FIG. 18 is an enlarged view of a portion of a carrier depicting one setof main conduit support rails and collars useful in isolating theprocess chambers on a sample processing device of the present invention.

FIG. 19 is a partial cross-sectional view of a portion of a carrierillustrating one example of a force transfer structure useful within thecarrier.

FIG. 19A is a partial cross-sectional view of a carrier and sampleprocessing device assembly including an optical element in the carrier.

FIG. 19B depicts a carrier and sample processing device assemblyincluding an alignment structure for a sample processing deliverydevice.

FIG. 20 is an exploded perspective view of an alternative sampleprocessing device and carrier assembly according to the presentinvention.

FIG. 20A is a block diagram of one thermal processing system that may beused in connection with the sample processing devices of the presentinvention.

FIG. 21 is a schematic diagram of one sealing apparatus that may be usedin connection with the present invention.

FIG. 22 is a perspective view of the apparatus of FIG. 21.

FIGS. 23-25 depict profiles of various sealing structures used toocclude conduits in connection with the apparatus of FIGS. 21 & 22.

FIGS. 26A-26F depict various seal structures useful in connection withsample processing devices of the present invention.

FIGS. 27A & 27B depict one seal including an expandable material used toocclude a conduit in a sample processing device of the presentinvention.

FIGS. 28A & 28B depict an alternative construction for an sampleprocessing device of the present invention including a core locatedbetween opposing sides.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS OF THE INVENTION

The present invention provides a sample processing device that can beused in the processing of liquid sample materials (or sample materialsentrained in a liquid) in multiple process chambers to obtain desiredreactions, e.g., PCR amplification, ligase chain reaction (LCR),self-sustaining sequence replication, enzyme kinetic studies,homogeneous ligand binding assays, and other chemical, biochemical, orother reactions that may, e.g., require precise and/or rapid thermalvariations. More particularly, the present invention provides sampleprocessing devices that include one or more process arrays, each ofwhich include a loading chamber, a plurality of process chambers and amain conduit placing the process chambers in fluid communication withthe loading chamber.

Although various constructions of illustrative embodiments are describedbelow, sample processing devices of the present invention may bemanufactured according to the principles described in U.S. ProvisionalPatent Application Ser. No. 60/214,508 filed on Jun. 28, 2000 and titledTHERMAL PROCESSING DEVICES AND METHODS (Attorney Docket No.55265USA19.003); U.S. Provisional Patent Application Ser. No. 60/214,642filed on Jun. 28, 2000 and titled SAMPLE PROCESSING DEVICES, SYSTEMS ANDMETHODS (Attorney Docket No. 55266USA99.003); U.S. Provisional PatentApplication Ser. No. 60/237,072 filed on Oct. 2, 2000 and titled SAMPLEPROCESSING DEVICES, SYSTEMS AND METHODS (Attorney Docket No.56047USA29); and U.S. Pat. No. 6,627,159, titled CENTRIFUGAL FILLING OFSAMPLE PROCESSING DEVICES.

The documents identified above all disclose a variety of differentconstructions of sample processing devices that could be used tomanufacture sample processing devices according to the principles of thepresent invention. For example, although many of the sample processingdevices described herein are attached using adhesives (e.g., pressuresensitive adhesives), devices of the present invention could bemanufactured using heat sealing or other bonding techniques.

One illustrative sample processing device manufactured according to theprinciples of the present invention is illustrated in FIGS. 1 and 2,where FIG. 1 is a perspective view of one sample processing device 10and FIG. 2 is an enlarged plan view of a portion of the sampleprocessing device. The sample processing device 10 includes at leastone, and preferably a plurality of process arrays 20. Each of thedepicted process arrays 20 extends from proximate a first end 12 towardsthe second end 14 of the sample processing device 10.

The process arrays 20 are depicted as being substantially parallel intheir arrangement on the sample processing device 10. Although thisarrangement may be preferred, it will be understood that any arrangementof process arrays 20 that results in their substantial alignment betweenthe first and second ends 12 and 14 of the device 10 may alternativelybe preferred.

Alignment of the process arrays 20 may be important if the main conduits40 of the process arrays are to be closed simultaneously as discussed inmore detail below. Alignment of the process arrays 20 may also beimportant if sample materials are to be distributed throughout thesample processing device by rotation about an axis of rotation proximatethe first end 12 of the device 10. When so rotated, any sample materiallocated proximate the first end 12 is driven toward the second end 14 bycentrifugal forces developed during the rotation.

Each of the process arrays 20 includes at least one main conduit 40, anda plurality of process chambers 50 located along each main conduit 40.The process arrays 20 also include a loading structure in fluidcommunication with a main conduit 40 to facilitate delivery of samplematerial to the process chambers 50 through the main conduit 40. It maybe preferred that, as depicted in FIG. 1, each of the process arraysinclude only one loading structure 30 and only one main conduit 40.

The loading structure 30 may be designed to mate with an externalapparatus (e.g., a pipette, hollow syringe, or other fluid deliveryapparatus) to receive the sample material. The loading structure 30itself may define a volume or it may define no specific volume, but,instead, be a location at which sample material is to be introduced. Forexample, the loading structure may be provided in the form of a portthrough which a pipette or needle is to be inserted. In one embodiment,the loading structure may be, e.g., a designated location along the mainconduit that is adapted to receive a pipette, syringe needle, etc.

The loading chamber depicted in FIG. 1 is only one embodiment of aloading structure 30 in fluid communication with the main conduit 40. Itmay be preferred that the loading chamber volume, i.e., the volumedefined by the loading chamber (if so provided), be equal to or greaterthan the combined volume of the main conduit 40, process chambers 50,and feeder conduits 42 (if any).

The process chambers 50 are in fluid communication with the main conduit40 through feeder conduits 42. As a result, the loading structure 30 ineach of the process arrays 20 is in fluid communication with each of theprocess chambers 50 located along the main conduit 40 leading to theloading structure 30. If desired, each of the process arrays 20 may alsoinclude an optional drain chamber (not shown) located at the end of themain conduit 40 opposite the loading structure 30.

If the loading structure 30 is provided in the form of a loadingchamber, the loading structure 30 may include an inlet port 32 forreceiving sample material into the loading structure 30. The samplematerial may be delivered to inlet port 32 by any suitable techniqueand/or equipment. A pipette 11 is depicted in FIG. 1, but is only onetechnique for loading sample material into the loading structures 30.The pipette 11 may be operated manually or may be part of an automatedsample delivery system for loading the sample material into loadingstructures 30 of sample processing device 10.

Each of the loading structures 30 depicted in FIG. 1 also includes avent port 34 with the loading structure 30. The inlet port 32 and thevent port 34 may preferably be located at the opposite ends of the legsof a U-shaped loading chamber as depicted in FIG. 1. Locating the inletport 32 and the vent port 34 at opposite ends of the legs of a U-shapedloading chamber may assist in filling of the loading structure 30 byallowing air to escape during filling of the loading structure 30.

It should be understood, however, that the inlet ports and vent ports inloading structures 30 are optional. It may be preferred to provideloading structures that do not include pre-formed inlet or vent ports.In such a device, sample material may be introduced into the loadingstructure by piercing the chamber with, e.g., a syringe. It may bedesirable to use the syringe or another device to pierce the loadingstructure in a one location before piercing the loading structure in asecond location to fill the chamber. The first opening can then serve asa vent port to allow air (or any other gas) within the loading structureto escape during loading of the sample material.

Some potential alternative loading structures 30′ and 30″ are depictedin FIGS. 2A and 2B, respectively. Loading structure 30′ includes aninlet port 32′ and a vent port 34′ in a generally wedge-shaped loadingchamber. Loading structure 30″ of FIG. 2B also includes an inlet port32″ and a vent port 34″ in addition to a baffle 36″ partially separatingthe loading chamber between the inlet port 32″ and the vent port 34″.The baffle 36″ may serve the same purpose as the separate legs of theU-shaped loading chamber depicted in FIG. 1. The baffle 36″ may take avariety of forms, for example, the baffle 36″ may be molded into thesame side of the device as the structure of the loading chamber 30″, thebaffle 36″ may be formed by attaching the sides of the device togetherwithin the loading chamber, etc.

Each of the process arrays 20 in the sample processing devices 10 of thepresent invention may preferably be unvented. As used in connection withthe present invention, an “unvented” process array is a process array inwhich the only ports leading into the volume of the process array arelocated in a loading chamber of the process array. In other words, toreach the process chambers within an unvented process array, samplematerials must be delivered through the loading structure. Similarly,any air or other fluid located within the process array before loadingwith sample material must also escape from the process array through theloading structure. In contrast, a vented process array would include atleast one opening outside of the loading structure. That opening wouldallow for the escape of any air or other fluid located within theprocess array before loading during distribution of the sample materialwithin the process array.

Methods of distributing sample materials by rotating a sample processingdevice about an axis of rotation located proximate the loadingstructures are described in U.S. Pat. No. 6,627,159, titled CENTRIFUGALFILLING OF SAMPLE PROCESSING DEVICES.

It may be preferred that, regardless of the exact method used to deliversample materials to the process chambers through the main conduits ofsample processing devices of the present invention, the result is thatsubstantially all of the process chambers, main conduit, and feederconduits (if any) are filled with the sample material.

The process arrays 20 depicted in FIG. 1 are arranged with the processchambers 50 located in two groups on both sides of each of the mainconduits 40. The process chambers 50 are in fluid communication with themain conduit 40 through feeder conduits 42. It may be preferred that theprocess chambers 50 be generally circular in shape and that the feederconduits 42 enter the process chambers 50 along a tangent. Such anorientation may facilitate filling of the process chambers 50.

The feeder conduits 42 are preferably angled off of the main conduit 40to form a feeder conduit angle that is the included angle formed betweenthe feeder conduit 42 and the main conduit 40. It may be preferred thatthe feeder conduit angle be less than 90 degrees, more preferably about45 degrees or less. The feeder conduit angles formed by the feederconduits 42 may be uniform or they may vary between the differentprocess chambers 50. In another alternative, the feeder conduit anglesmay vary between the different sides of each of the main conduits 40.For example, the feeder conduit angles on one side of each of the mainconduits 40 may be one value while the feeder conduit angles on theother side of the main conduits may be a different value.

Each of the feeder conduits 42 connects to the main conduit 40 at afeeder conduit junction 43. It may be preferred that the feeder conduitjunctions 43 for the different process chambers 50 be offset along thelength of the main conduit such that no two feeder conduit junctions arelocated directly across from each other. Such a construction may enhanceisolation between the process chambers 50 during thermal processing ofsample materials in the different process chambers by providing a longerdiffusion path length between the process chambers 50.

FIGS. 3A-3D depict a variety of different feeder conduit and processchamber arrangements that may be used in connection with the processarrays of the present invention. The variations between arrangements maybe found in the shape of the process chambers, how the feeder conduitsenter the process chambers, the feeder conduit angles, and whether thefeeder conduit junctions with the main conduit are aligned or offset,etc.

Turning to FIG. 3A, the process chambers 50 a are connected to the mainconduit 40 a through feeder conduits 42 a. The feeder conduits 42 a areconnected to the main conduit 40 a at feeder conduit junctions 43 a thatare located directly opposite from each other across the main conduit 40a. In addition, the feeder conduits 42 a enter the process chambersalong a line that is not aligned with a tangent of the circular processchambers 50 a. In the depicted embodiment, the centerline of each feederconduit 42 a is aligned with the center of the circular process chambers50 a, although such an arrangement is not required.

FIG. 3B depicts another arrangement of process chambers and feederconduits that is similar in many respects to the arrangement of processchambers 50 a and feeder conduits 42 a depicted in FIG. 3A. Onedifference is that the feeder conduits 42 b of FIG. 3B enter thecircular process chambers 50 b along a tangent to each of the processchambers 50 b. One potential advantage of arranging the feeder conduitsalong a tangent to the process chambers 50 b may include increasing thelength of the feeder conduits 42 b (which may improve isolation of theprocess chambers 50 b). Another potential advantage is that entry ofliquid sample materials along a tangent to the process chamber 50 b mayenhance mixing of the sample materials with any reagents or otherconstituents located within the process chamber 50 b.

Another alternative arrangement of process chambers and feeder conduitsis depicted in FIG. 3C where the feeder conduits 42 c enter the processchambers 50 c along tangents to the generally circular process chambers50 c. One difference with the arrangement depicted in FIG. 3B is thatthe feeder conduit junctions 43 c (the points at which the feederconduits 42 c connect with the main conduit 40 c) are offset along thelength of the main conduit 40 c. As discussed above, that offset of thefeeder conduit junctions 43 c may enhance process chamber isolation.

FIG. 3C also depicts another optional feature in the feeder conduitangles, i.e., that included angle formed between the feeder conduits 42c and the main conduit 40 c. In FIG. 3C, the feeder conduit angle α(alpha) formed on the left side of the main conduit 40 c is differentthan the feeder conduit angle β (beta) formed on the right side of themain conduit 40 c. More specifically, the left-side feeder conduit angleα is less than the right-side feeder conduit angle β. The differentfeeder conduit angles may be useful to offset the feeder conduitjunctions 43 c when the process chambers 50 c are located directlyopposite each other across the main conduit 40 c. Potential combinationsof different feeder conduit angles may be, e.g., 25 degrees on one sideand 45 degrees on the opposite side, although the particular angleschosen will vary based on a variety of factors including, but notlimited to, size of the process chambers, distance between the processchambers, distance between the feeder conduit junctions with the mainconduit, etc.

FIG. 3D depicts another arrangement of feeder conduits and processchambers that may be used within process arrays on sample processingdevices according to the present invention. Although the processchambers illustrated in FIGS. 3A-3C are generally circular in shape, itshould be understood that the process chambers used in sample processingdevices of the present invention may take any suitable shape. Oneexample of an alternative shape is depicted in FIG. 3D in which theprocess chambers 50 d are in the form of oval shapes that are elongatedalong axis 51 d. The axis 51 d is preferably generally aligned with themain conduit 40 d. As a result, the oval-shaped process chambers 50 dhave their largest dimension aligned with the main conduit 40 d.

FIG. 3D also depicts feeder conduits 42 d that are preferably angled offof the main conduit 40 d and adjoin the process chambers 50 d at oneend. It may be further preferred that the feeder conduits 42 d meet theprocess chambers 50 d at the end closest to the loading structures (notshown). Entry of the feeder conduits 42 d into the process chambers 50 dat the end may facilitate removal of air within the chambers 50 d duringdistribution of sample material.

FIGS. 4 and 5, in conjunction with FIG. 2, illustrate yet anotheroptional feature of the sample processing devices of the presentinvention. FIG. 4 is a cross-sectional view of FIG. 2 taken along line4-4 in FIG. 2 and FIG. 5 is a cross-sectional view of FIG. 2 taken alongline 5-5 in FIG. 4.

It may be preferred to maintain the size of both the main conduit 40 andthe feeder conduit 42 as small as possible while still allowing foradequate sample material delivery and sufficient distance between theprocess chambers 50 to limit diffusion. Reducing the size of theconduits 40 and 42 limits “conduit volume” within the process arrays,where conduit volume is the combined volume of the main conduit 40 andthe feeder conduits 42 (where present), i.e., conduit volume does notinclude the volume of the process chambers 50. It may be desirable tolimit the ratio of conduit volume to the total process chamber volume(i.e., the combined volume of all of the process chambers in the subjectprocess array) to about 2:1 or less, alternatively about 1:1 or less.

One manner in which conduit volume can be limited is to reduce thecross-sectional area of the main conduit 40 and/or the feeder conduits42 (if present in the device). It may be possible to provide feederconduits 42 with a smaller cross-sectional area than the main conduit 40because of the reduced length of the feeder conduits 42 as compared tothe main conduit 40 (making flow restriction less of a concern in thefeeder conduits). FIGS. 4 & 5 depict the smaller cross-sectional area ofthe feeder conduit 42 as compared to the main conduit 40. The differentcross-sectional area of the conduits 40 and 42 is achieved, in theillustrated embodiment, by different heights and widths in the twoconduits, although different cross-sectional areas may be achieved byvarying only one of height or width in the different conduits. It mayfurther be preferred that the height of both the main conduit 40 andfeeder conduits 42 (if provided) be less than the height of the processchambers 50 as seen in FIG. 4.

It may be preferred that all of the structures forming the conduits andprocess chambers be provided in the first side 16 while the second side18 is provided in the form of a generally flat sheet. In such a device,height of the conduits and process chambers can be measured above thegenerally flat second side 18.

FIG. 4 also depicts that process chamber 50 may include a reagent 54. Itmay be preferred that at least some, and preferably all, of the processchambers 50 in the devices 10 of the present invention contain at leastone reagent before any sample material is distributed. The reagent 54may be fixed within the process chamber 50 as depicted in FIG. 4. Thereagent 54 is optional, i.e., sample processing devices 10 of thepresent invention may or may not include any reagents 54 in the processchambers 50. In another variation, some of the process chambers 50 mayinclude a reagent 54, while others do not. In yet another variation,different process chambers 50 may contain different reagents.

The process chamber 50 also defines a volume 52. In sample processingdevices of the present invention, it may be preferred that the volume 52of the process chambers be about 5 microliters or less, alternativelyabout 2 microliters or less, and, in yet another alternative, about 1microliter or less. Providing sample processing devices withmicro-volume process chambers may be advantageous to reduce the amountof sample material required to load the devices, reduce thermal cyclingtime by reducing the thermal mass of the sample materials, etc.

Other features of the sample processing device 10 depicted in FIGS. 4and 5 are a first side 16 and a second side 18, between which the volume52 of process chamber 50 is formed. In addition to the process chambers50, the main conduit 40 and the feeder conduits 42 are also formedbetween the first and second sides 16 and 18. Although not depicted, theloading structures, e.g., loading structures, are also formed betweenthe first and second sides 16 and 18 of the sample processing device 10.

The major sides 16 and 18 of the device 10 may be manufactured of anysuitable material or materials. Examples of suitable materials includepolymeric materials (e.g., polypropylene, polyester, polycarbonate,polyethylene, etc.), metals (e.g., metal foils), etc. In one embodiment,it may be preferred to provide all of the features of the processarrays, such as the loading structures, main conduits, feeder conduitsand process chambers in one side of the device, while the opposite sideis provided in a generally flat sheet-like configuration. For example,it may be preferred to provide all of the features in the first side 16in a polymeric sheet that has been molded, vacuum-formed, or otherwiseprocessed to form the process array features. The second side 18 canthen be provided as, e.g., a sheet of metal foil, polymeric material,multi-layer composite, etc. that is attached to the first side tocomplete formation of the process array features. It may be preferredthat the materials selected for the sides of the device exhibit goodwater barrier properties.

By locating all of the features in one side of the sample processingdevice 10, the need for aligning the two sides together before attachingthem may be eliminated. Furthermore, providing the sample processingdevice 10 with a flat side may promote intimate contact with, e.g., athermal block (such as that used in some thermal cycling equipment). Inaddition, by providing all of the features in one side of the sampleprocessing device, a reduced thermal mass may be achieved for the sameprocess chamber volume. Further, the ability to selectively compressdiscrete areas about each of the process chambers may be enhanced indevices in which the structure is found on only one side thereof.Alternatively, however, it will be understood that features may beformed in both sides 16 and 18 of sample processing devices according tothe present invention.

It may be preferred that at least one of the first and second sides 16and 18 be constructed of a material or materials that substantiallytransmit electromagnetic energy of selected wavelengths. For example, itmay be preferred that one of the first and second sides 16 and 18 beconstructed of a material that allows for visual or machine monitoringof fluorescence or color changes within the process chambers 50.

It may also be preferred that at least one of the first and second sides16 and 18 include a metallic layer, e.g., a metallic foil. If providedas a metallic foil, the side may include a passivation layer on thesurfaces that face the interiors of the loading structures 30, mainconduits 40, feeder conduits 42, and/or process chambers 50 to preventcontamination of the sample materials by the metal.

As an alternative to a separate passivation layer, any adhesive layer 19used to attached the first side 16 to the second side 18 may also serveas a passivation layer to prevent contact between the sample materialsand any metallic layer in the second side 18. The adhesive may also bebeneficial in that it may be conformable. If so, the adhesive mayprovide enhanced occlusion by filling and/or sealing irregularities orsurface roughness' present on either of the two sides.

In the illustrative embodiment of the sample processing device depictedin FIGS. 1 and 2, the first side 16 is preferably manufactured of apolymeric film (e.g., polypropylene) that is formed to providestructures such as the loading structures 30, main conduit 40, feederconduits 42, and process chambers 50. The second side 18 is preferablymanufactured of a metallic foil, e.g., an aluminum or other metal foil.The metallic foil is preferably deformable as discussed in more detailbelow.

The first and second sides 16 and 18 may be attached to each other byany suitable technique or techniques, e.g., melt bonding, adhesives,combinations of melt bonding and adhesives, etc. If melt bonded, it maybe preferred that both sides 16 and 18 include, e.g., polypropylene orsome other melt bondable material, to facilitate melt bonding. It may,however, be preferred that the first and second sides 16 and 18 beattached using adhesive. As depicted in FIGS. 4 and 5, the adhesive maypreferably be provided in the form of a layer of adhesive 19. It may bepreferred that the adhesive layer 19 be provided as a continuous,unbroken layer over the surface of at least one of the first and secondsides 16 and 18. It may, for example, be preferred that the adhesivelayer 19 be provided on the second side 18 and, more particularly, itmay be preferred that the adhesive layer 19 cover substantially all ofthe surface of the second side 18 facing the first side 16.

A variety of adhesives may be used, although any adhesive selectedshould be capable of withstanding the forces generated during processingof any sample materials located in the process chambers 50, e.g., forcesdeveloped during distribution of the sample materials, forces developedduring thermal processing of the sample materials, etc. Those forces maybe large where e.g., the processing involves thermal cycling as in,e.g., polymerase chain reaction and similar processes. It may also bepreferred that any adhesives used in connection with the sampleprocessing devices exhibit low fluorescence, be compatible be theprocesses and materials to be used in connection with sample processingdevices, e.g. PCR, etc.

It may be preferred to use adhesives that exhibit pressure sensitiveproperties. Such adhesives may be more amenable to high volumeproduction of sample processing devices since they typically do notinvolve the high temperature bonding processes used in melt bonding, nordo they present the handling problems inherent in use of liquidadhesives, solvent bonding, ultrasonic bonding, and the like.

One well known technique for identifying pressure sensitive adhesives isthe Dahlquist criterion. This criterion defines a pressure sensitiveadhesive as an adhesive having a 1 second creep compliance of greaterthan 1×10⁻⁶ cm²/dyne as described in Handbook of Pressure SensitiveAdhesive Technology, Donatas Satas (Ed.), 2^(nd) Edition, p. 172, VanNostrand Reinhold, New York, N.Y., 1989. Alternatively, since modulusis, to a first approximation, the inverse of creep compliance, pressuresensitive adhesives may be defined as adhesives having a Young's modulusof less than 1×10⁶ dynes/cm². Another well known means of identifying apressure sensitive adhesive is that it is aggressively and permanentlytacky at room temperature and firmly adheres to a variety of dissimilarsurfaces upon mere contact without the need of more than finger or handpressure, and which may be removed from smooth surfaces without leavinga residue as described in Test Methods for Pressure Sensitive AdhesiveTapes, Pressure Sensitive Tape Council, (1996). Another suitabledefinition of a suitable pressure sensitive adhesive is that itpreferably has a room temperature storage modulus within the areadefined by the following points as plotted on a graph of modulus versusfrequency at 25° C.: a range of moduli from approximately 2×10⁵ to 4×10⁵dynes/cm² at a frequency of approximately 0.1 radian/second (0.017 Hz),and a range of moduli from approximately 2×10⁶ to 8×10⁶ dynes/cm² at afrequency of approximately 100 radians/second (17 Hz) (for example seeFIG. 8-16 on p. 173 of Handbook of Pressure Sensitive AdhesiveTechnology, Donatas Satas (Ed.), 2^(nd) Edition, Van Nostrand Rheinhold,New York, 1989). Any of these methods of identifying a pressuresensitive adhesive may be used to identify potentially suitable pressuresensitive adhesives for use in the methods of the present invention.

It may be preferred that the pressure sensitive adhesives used inconnection with the sample processing devices of the present inventioninclude materials which ensure that the properties of the adhesive arenot adversely affected by water. For example, the pressure sensitiveadhesive will preferably not lose adhesion, lose cohesive strength,soften, swell, or opacify in response to exposure to water during sampleloading and processing. Also, the pressure sensitive adhesive should notcontain any components which may be extracted into water during sampleprocessing, thus possibly compromising the device performance.

In view of these considerations, it may be preferred that the pressuresensitive adhesive be composed of hydrophobic materials. As such, it maybe preferred that the pressure sensitive adhesive be composed ofsilicone materials. That is, the pressure sensitive adhesive may beselected from the class of silicone pressure sensitive adhesivematerials, based on the combination of silicone polymers and tackifyingresins, as described in, for example, “Silicone Pressure SensitiveAdhesives”, Handbook of Pressure Sensitive Adhesive Technology, 3^(rd)Edition, pp. 508-517. Silicone pressure sensitive adhesives are knownfor their hydrophobicity, their ability to withstand high temperatures,and their ability to bond to a variety of dissimilar surfaces.

The composition of the pressure sensitive adhesives is preferably chosento meet the stringent requirements of the present invention. Somesuitable compositions may be described in International Publication WO00/68336 titled SILICONE ADHESIVES, ARTICLES, AND METHODS (Ko et al.).

Other suitable compositions may be based on the family ofsilicone-polyurea based pressure sensitive adhesives. Such compositionsare described in U.S. Pat. No. 5,461,134 (Leir et al.); U.S. Pat. No.6,007,914 (Joseph et al.); International Publication No. WO 96/35458(and its related U.S. Patent application Ser. No. 08/427,788 (filed Apr.25, 1995); U.S. Patent application Ser. No. 08/428,934 (filed Apr. 25,1995); U.S. Patent application Ser. No. 08/588,157 (filed Jan. 17,1996); and U.S. Patent application Ser. No. 08/588,159 (filed Jan. 17,1996); International Publication No. WO 96/34028 (and its related U.S.Patent application Ser. No. 08/428,299 (filed Apr. 25, 1995); U.S.Patent application Ser. No. 08/428,936 (filed Apr. 25, 1995); U.S.Patent application Ser. No. 08/569,909 (filed Dec. 8, 1995); and U.S.Patent application Ser. No. 08/569,877 (filed Dec. 8, 1995)); andInternational Publication No. WO 96/34029 (and its related U.S. Patentapplication Ser. No. 08/428,735 (filed Apr. 25, 1995) and U.S. Patentapplication Ser. No. 08/591,205 (filed Jan. 17, 1996)).

Such pressure sensitive adhesives are based on the combination ofsilicone-polyurea polymers and tackifying agents. Tackifying agents canbe chosen from within the categories of functional (reactive) andnonfunctional tackifiers as desired. The level of tackifying agent oragents can be varied as desired so as to impart the desired tackiness tothe adhesive composition. For example, it may be preferred that thepressure sensitive adhesive composition be a tackifiedpolydiorganosiloxane oligurea segmented copolymer including (a) softpolydiorganosiloxane units, hard polyisocyanate residue units, whereinthe polyisocyanate residue is the polyisocyanate minus the —NCO groups,optionally, soft and/or hard organic polyamine units, wherein theresidues of isocyanate units and amine units are connected by urealinkages; and (b) one or more tackifying agents (e.g., silicate resins,etc.).

Furthermore, the pressure sensitive layer of the sample processingdevices of the present invention can be a single pressure sensitiveadhesive or a combination or blend of two or more pressure sensitiveadhesives. The pressure sensitive layers may result from solventcoating, screen printing, roller printing, melt extrusion coating, meltspraying, stripe coating, or laminating processes, for example. Anadhesive layer can have a wide variety of thicknesses as long as itmeets exhibits the above characteristics and properties. In order toachieve maximum bond fidelity and, if desired, to serve as a passivationlayer, the adhesive layer should be continuous and free from pinholes orporosity.

Even though the sample processing devices may be manufactured with apressure sensitive adhesive to connect the various components, e.g.,sides, together, it may be preferable to increase adhesion between thecomponents by laminating them together under elevated heat and/orpressure to ensure firm attachment of the components and sealing of theprocess arrays.

Another potential feature of the sample processing devices of theinvention is a deformable seal that may be used to close the mainconduit, isolate the process chambers 50, or accomplish both closure ofthe main conduit and isolation of the process chambers. As used inconnection with the present invention, the deformable seals may beprovided in a variety of locations and/or structures incorporated intothe sample processing devices. Essentially, however, the deformable sealin a process array will be located somewhere in the fluid path betweenthe loading chamber and the plurality of process chambers.

With respect to FIG. 1, for example, the deformable seal may be locatedin the main conduit 40 between the loading structure 30 and theplurality of process chambers 50 of each process array 20. In thisconfiguration the deformable seal may extend for the substantially theentire length of the main conduit 40 or it may be limited to selectedareas. For example, the deformable seal may extend along the mainconduit 40 only in the areas occupied by the feeder conduits 42 leadingto the process chambers 50. In another example, the deformable seal maybe a composite structure of discrete sealing points located along themain conduit 40 or within each of the feeder conduits 42. Referring toFIG. 7 (described below), in another configuration, the deformable sealmay be limited to the area 119 between the loading structures 130 andthe plurality of process chambers 150 in each of the process arrays 120.

Closure of the deformable seals may involve plastic deformation ofportions of one or both sides 16 and 18 to occlude the main conduits 40and/or feeder conduits 42. If, for example, a pressure sensitiveadhesive 19 is used to attach the first and second sides 16 and 18 ofthe sample processing device together, that same pressure sensitiveadhesive may help to maintain occlusion of the main conduits 40 and/orfeeder conduits 42 by adhering the deformed first and second sides 16and 18 together. In addition, any conformability in the adhesive 19 mayallow it to conform and/or deform to more completely fill and occludethe main conduits 40 and/or feeder conduits 42.

It should be understood, however, that complete sealing or occlusion ofthe deformed portions of the sample processing device 10 may not berequired. For example, it may only be required that the deformationrestrict flow, migration or diffusion through a conduit or other fluidpathway sufficiently to provide the desired isolation. As used inconnection with the present invention, “occlusion” will include bothpartial occlusion and complete occlusion (unless otherwise explicitlyspecified). Furthermore, occlusion of the main conduit may becontinuously over substantially all of the length of the main conduit orit may be accomplished over discrete portions or locations along thelength of the main conduit. Also, closure of the deformable seal may beaccomplished by occlusion of the feeder conduits alone and/or byocclusion of the feeder conduit/main conduit junctions (in place of, orin addition to, occlusion of a portion or all of the length of the mainconduit).

In some embodiments in which the deformable seal is provided in the formof an occludable main conduit, it may be advantageous to occlude themain conduit over substantially all of its length and, in so doing, urgeany sample materials within the main conduit back towards the loadingchamber (e.g., as described below in connection with FIGS. 21-25). Itmay be preferred that the sample materials urged back towards theloading chamber are driven back into the loading chamber. As a result,the loading chambers in process arrays of the present invention may alsoserve as waste or purge chambers for sample materials urged out of themain conduits and/or feeder conduits during closure of the deformableseals.

Referring now to FIGS. 4-6, one embodiment of a deformable seal forisolating the process chambers 50 is depicted. The deformable seal isprovided in the form of a deformable second side 18 that can be deformedsuch that it extends into the main conduit 40 as depicted in FIG. 6.

The use of adhesive to attach the first side 16 to the second side 18may enhance closure or occlusion of the deformable seal by adhering thetwo sides together within the main conduit 40. It may be preferred thatthe adhesive 19 be a pressure sensitive adhesive in such an embodiment,although a hot melt adhesive may alternatively be used if deformation ofthe main conduit 40 is accompanied by the application of thermal energysufficient to activate the hot melt adhesive.

In one method in which the process arrays 20 are closed afterdistribution of sample materials into process chambers 50, it may benecessary to close the deformable seal along only a portion of the mainconduit 40 or, alternatively, the entire length of the distributionchannel 40. Where only a portion of the main conduit 40 is deformed, itmay be preferred to deform that portion of the main conduit 40 locatedbetween the loading chamber 30 and the process chambers 50.

Sealing all of the main conduit 40 by forcing the sides 16 and 18together along the length of the conduit 40 may provide advantages suchas driving any fluid located in the main conduit 40 back into theloading structure 30. One potential advantage, however, of sealing onlya portion of the length of the main conduit 40 is that either none oronly a small amount of any fluid material located in the main conduit 40would be returned to the loading structure 30.

FIGS. 7 & 8 depict another sample processing device 110 according to thepresent invention that includes a first side 116 attached to a secondside 118, with a set of process arrays 120 formed between the two sides116 and 118. One difference between the sample processing device 110depicted in FIGS. 7 & 8 and the sample processing device of FIGS. 1 & 2is that the sides 116 and 118 of the sample processing device 110 areattached together by the combination of a melt bond and an adhesive.

As used herein, a “melt bond” is a bond formed by the melting and/ormixing of materials such as that occurring during, e.g., heat sealing,thermal welding, ultrasonic welding, chemical welding, solvent bonding,etc. In such a device, the materials facing each other in sides 116 and118 must be compatible with melt bonding so that a seal of sufficientintegrity can be formed to withstand the forces experienced duringprocessing of sample materials in the process chambers.

The adhesive 119 is provided only within a selected area of the sampleprocessing device and may be provided for the dual purpose of attachingportions of the two sides 116 and 118 together and assisting withsealing or occlusion of the main conduit 140 by adhering the sides 116and 118 together as discussed above.

It may be preferred that the selected area of pressure sensitiveadhesive 119 be located between the loading chambers 130 and the processchambers 150 as seen in FIGS. 7 & 8. Although the pressure sensitiveadhesive 119 is depicted as being limited to an area that does notinclude the loading chambers 130, it should be understood that thepressure sensitive adhesive 119 may be used to attach the two sides 116and 118 together within the area occupied by the loading chambers 130 inaddition to the area between the loading structures 130 and the processchambers 150.

By locating the pressure sensitive adhesive 119 in the area between theloading structures 130 and the process chambers 150, the main conduits140 are directed through the pressure sensitive adhesive layer 119 suchthat closure or occlusion of the deformable seals can be assisted by theadhesive located between the two sides 116 and 118. Another potentialadvantage of attaching the two sides 116 and 118 together with a meltbond in the area occupied by the process chambers 150 is that the bondstrength of the melt bond may be better suited to withstand the forcesdeveloped during thermal processing of sample materials in the processchambers 150.

FIG. 7 also depicts another arrangement of process arrays 120 that maybe used in connection with sample processing devices of the presentinvention. Each of the process arrays 120 includes a loading structure130. The loading structures 130 are in fluid communication with aplurality of process chambers 150 through main conduits 140.

One feature illustrated in connection with FIG. 7 is the addition ofvalves 144 along the main conduits 140. By selectively opening orclosing the valves 144 along the main conduit 140 (which may be eitherclosed or open when manufactured) the delivery of sample material toeach set of process chambers 150 may be enabled or prevented. Forexample, if one of the valves 144 is open while the other valve 144 isclosed, delivery of sample material will be effected only to one set ofprocess chambers 150 (through the open valve 144).

It may be possible to achieve the same result, i.e., enabling orpreventing delivery of sample material to a subset of process chambers150, by sealing the main conduit 140 at an appropriate location afterthe bifurcation point. The use of valves 144 may, however, provided theability for automated control or customization of the sample processingdevice including process arrays 120. The valves 144 may take anysuitable form, some examples of which are described in the patentapplications identified above.

By using customizable process arrays 120, it may be possible to providesample processing devices that are tailored at the point of use forparticular testing needs. Other advantages may be found in the abilityto reduce the volume of sample material needed by reducing the number ofprocess chambers 150 to which that sample material may be delivered.Alternatively, where a higher level of confidence is required, thevalves 144 may be opened to increase the number of process chambers 150to which sample material is delivered, thereby increasing the number oftests performed.

FIGS. 9 & 10 depict another sample processing device 210 according tothe present invention that includes a first side 216 attached to asecond side 218, with a set of process arrays 220 formed between the twosides 216 and 218. One difference between the sample processing device110 depicted in FIGS. 7 & 8 and the sample processing device 210 ofFIGS. 9 & 10 is that the sides 216 and 218 of the sample processingdevice 210 are attached together by a melt bond.

FIG. 9 also depicts another arrangement for process arrays 220 useful insample processing devices of the invention. Among the features depictedin connection with process arrays 220 are the staggered relationshipbetween loading structures 230. Such a staggered relationship may allowfor a higher density of process chambers 250 on the sample processingdevice.

Each of the loading structures 230 also includes a loading port 232 anda vent port 234 which may facilitate rapid filling of the loadingstructures 230 by providing a pathway separate from the loading port 232for air to escape during filling of the loading structure 230.

Another feature depicted in FIG. 9 is the serial relationship betweenthe process chambers 250 located along each of the main conduits 240.Each pair of successive process chambers 250 is in fluid communicationwith each other along main conduit 240. As a result, if any reagents orother materials are to be located within process chambers 250 beforedistribution of the sample material, then some mechanism or techniquefor preventing removal of those materials during distribution of thesample material must be provided. For example, the reagents may becontained in a wax or other substance within each of the processchambers 250.

Furthermore, it may be preferred that the height of the main conduits240 between the process chambers 250 be less than the height of theprocess chambers 250. Such a design may improve the ability to rapidlyand accurately occlude the main conduits by deforming a deformable sealstructure located within the main conduits 240.

FIG. 11 depicts yet another arrangement of process arrays 320 on asample processing device 310 in which the process arrays 320 share acommon loading structure 330 from which a set of main conduits 340extend. Each of the main conduits 340 connects a set of process chambers350 to the common loading structure 330.

Another feature in the process arrays 320 of sample processing device310 are drain chambers 360 connected to the end of the main conduits 340that is opposite the loading structure 330. The drain chambers 360 maybe separated from the main conduit by a drain valve 362 that maypreferably be closed until the process chambers 350 are filled withsample material. After filling of the process chambers 350, the drainvalve 362 can be opened to allow sample material remaining in the mainconduits 340 and loading structure 330 to proceed into the drain chamber360. The drain chambers 360 may allow for improved sealing or occlusionof the main conduits 340 by providing for the removal of samplematerials from the main conduits 340 before sealing as discussed above.

Referring now to FIG. 12, another optional feature of the presentinvention is separation of the loading structures 430 from the remainderof another embodiment of a sample processing device 410 according to thepresent invention. Separation of the loading portion of the sampleprocessing device 410 from the portion containing the process chambers450 may provide advantages such as, for example, reducing the size ofthe sample processing device 410, reducing the thermal mass of thesample processing device 410, removing any sample materials that mayremain within the loading structures 430 after distribution to processchambers 450, etc.

Separation of the loading structures 430 from the sample processingdevice 410 may involve, for example, cutting the sample processingdevice 410 along the separation line 413 as depicted in FIG. 12. Wherethe loading structures 430 are to be physically separated from theremainder of the sample processing device 410, it is typicallypreferable that the main conduits 440 be sealed across at least theseparation line 413 to prevent leakage of the sample materials duringand after the separation process.

The use of an adhesive within the main conduits 440 (see, e.g., FIGS. 2and 3) may be particularly helpful to ensure adequate sealing of themain conduits 440 as discussed above. If additional sealing is required,it may also be helpful to cover the ends of the main conduits with aseal 444 as illustrated in FIG. 13. The seal 444 may be provided, e.g.,in the form of an adhesive coated foil or other material. Alternativelyor in addition to the use of an adhesive to secure the seal 444, it maybe desirable to, e.g., heat seal the seal 444 in place on the sampleprocessing device 410.

Referring now to FIGS. 14 and 15, one alternative to physical separationof the loading structures 530 from the remainder of the sampleprocessing device 510 may include folding the sample processing device510 along, e.g., separation line 513. That folding process may alsoclose the main conduit 540 across the separation line 513 by crimpingthe main conduits 540, such that a desired level isolation may beachieved between the process chambers 550 without further deformation ofany of the main conduits 540 or the feeder conduits 542.

It may be desirable to provide crimping areas 546 located at theintersections of the main conduits 540 with the folding line 513 thatare wider and shallower than the surrounding portions of conduits 540 tofacilitate crimping of the conduits 540 during folding. The wider,shallower crimping areas 546 do, however, preferably provide across-sectional area for fluid flow that is similar to thecross-sectional fluid flow area of the surrounding portions of the mainconduits 540.

Sample processing devices may be processed alone, e.g., as depicted inFIG. 1. It may, however, be preferred to provide the sample processingdevice 610 mounted on a carrier 680. Such an assembly is depicted in anexploded perspective view of sample processing device 610 and carrier680 in FIG. 16.

By providing a carrier that is separate from the sample processingdevice, the thermal mass of the sample processing device can beminimally affected as compared to manufacturing the entire sampleprocessing device with a thickness suitable for handling with automatedequipment (e.g., robotic arms, etc.) processing in conventionalequipment. Another potential advantage of a carrier is that the sampleprocessing devices may exhibit a tendency to curl or otherwise deviatefrom a planar configuration. Attaching the sample processing device to acarrier can retain the sample processing device in a planarconfiguration for processing.

Carriers used in connection with the sample processing devices of theinvention preferably also have some preferred physical properties. Forexample, it may be preferred that the carriers provide limited areas ofcontact with the sample processing devices to which they are mounted toreduce thermal transmission between the sample processing device and thecarrier. It may further be preferred that the surface of the carrierfacing away from the sample processing device also provide limited areasof contact with, e.g., a platen or other structure used to force thesample processing device against a thermal block to reduce thermaltransmission between the carrier and the platen or other structure. Itmay further be preferred that the carriers themselves have a relativelylow thermal mass to avoid influencing temperature changes in the sampleprocessing devices.

Another potentially desirable physical property of carriers manufacturedaccording to the present invention is that they exhibit some compliancesuch that the carrier (and attached sample processing device) canconform to the surfaces between which the assembly is compressed, e.g.,a thermal block and platen. Carriers themselves may not be perfectlyplanar due to, e.g., variations in manufacturing tolerances, etc.Further, the assemblies may have different thicknesses due to thicknessvariations in the carrier and/or the sample processing device.

If the sample processing device 610 is to be loaded using centrifugalforces developed during rotation of the sample processing devices thecentrifugal forces may challenge the sealing of the process chambers andother fluid pathways in each of the process arrays. The challenges maybe especially acute when the sample processing device is constructedusing an adhesive to attach to layers together. A properly designedcarrier may assist in maintaining the integrity of the sample processingdevice by providing the opportunity to apply pressure to the card duringloading and/or thermal cycling.

The carrier 680 may be attached to the sample processing device 610 in amanner that allows for the carrier 680 to be reused with many differentsample processing devices 610. Alternatively, each carrier 680 may bepermanently attached to a single sample processing device 610 such that,after use, both the sample processing device 610 and the carrier 680 arediscarded together.

In the depicted embodiment, the sample processing device 610 includesmolded posts 611 for aligning the sample processing device 610 to thecarrier. It may be preferred that at least one of the molded posts belocated proximate a center of the sample processing device 610. Althoughit may be possible to provide only one molded post 611 for attaching thesample processing device 610 to the carrier 680, it may be preferredthat at least two posts 611 be provided. The centrally-located post 611may assist in centering the sample processing device 610 on the carrier680, while the second post 611 may prevent rotation of the sampleprocessing device 610 relative to the carrier 680. Further, althoughonly two posts 611 are depicted, it will be understood that three ormore posts or other sites of attachment between the sample processingdevices 610 and the carriers 680 may be provided if desired. Further,the posts 611 may be melt bonded to the sample processing device 610 toalso accomplish attachment of the two components in addition toalignment.

Posts or other alignment features may also be provided on the, e.g., thecarrier 680 to generally align the sample processing device 610 on thecarrier 680 before the final alignment and attachment using molded posts611 on the sample processing device 610. The posts or other alignmentfeatures may also assist in aligning the assembly including the sampleprocessing device 610 and carrier 680 relative to, e.g., a thermalprocessing system used to thermally cycle materials in the sampleprocess chambers 650. Alignment may also be used in connection with adetection system for detecting the presence or absence of a selectedanalyte in the process chambers 650.

The carrier 680 may include various features such as openings 682 thatare preferably aligned with the process chambers 650 of the sampleprocessing device 610. By providing openings 682, the process chambers650 can be viewed through the carrier 680. One alternative to providingthe openings 682 is to manufacture the carrier 680 of a material (ormaterials) transmissive to electromagnetic radiation in the desiredwavelengths. As a result, it may be possible to use a carrier 680 thatis continuous over the surface of the sample processing device 610,i.e., a carrier with no openings formed therethrough for access to theprocess chambers 650.

The sample processing device 610 and carrier 680 are depicted attachedin FIG. 17, where it can be seen that the loading chambers 630 maypreferably extend beyond the periphery of the carrier 680. As such, theportion of the sample processing device 610 containing the loadingstructures 630 may be removed from the remainder of the sampleprocessing device 610 after distributing the sample material to theprocess chambers 650.

The carrier 680 illustrated in FIGS. 16 and 17 may also provideadvantages in the sealing or isolation of the process chambers 650during and/or after loading of sample materials in the process chambers650.

FIG. 18 is an enlarged view of a portion of the bottom surface of thecarrier 680, i.e., the surface of the carrier 680 that faces the sampleprocessing device 610. The bottom surface of the carrier 680 includes anumber of features including main conduit support rails 683 thatpreferably extend along the length of the main conduits 640 in theassociated sample processing device 610. The support rails 683 may, forexample, provide a surface against which the main conduits 640 of thesample processing device 610 may be pressed while the conduit 640 isdeformed to isolate the process chambers 650 and/or seal the conduits640 as discussed above.

In addition to their use during deformation of the main conduits 640,the support rails 683 may also be relied on during, e.g., thermalprocessing to apply pressure to the conduits 640. Furthermore, the useof support rails 683 also provides an additional advantage in that theyprovide for significantly reduced contact between the sample processingdevice 610 and the carrier 680 while still providing the necessarysupport for sealing of the main conduits 640 on device 610.

The importance of reducing contact between the carrier 680 and device610 may be particularly important when the assembly is to be used inthermal processing of sample materials (e.g., polymerase chain reaction,etc.). As such, the carrier 680 may be characterized as including acarrier body that is spaced from the sample processing device 610between the main conduits 640 when the support rails 683 are alignedwith the main conduits 640. The voids formed between the carrier bodyand the sample processing device 610 may be occupied by air or by, e.g.,a compressible and/or thermally insulating material.

Also depicted in FIG. 18 are a number of optional compression structures684 which, in the depicted embodiment, are in the form of collarsarranged to align with the process chambers 650 on the sample processingdevice 610. The collars define one end of each of the openings 682 thatextend through the carrier 680 to allow access to the process chambers650 on sample processing device 610. The compression structures 684,e.g., collars, are designed to compress a discrete area of the deviceproximate each of the process chambers 650 on the sample processingdevice 610 when the two components (the sample processing device 610 andthe carrier 680) are compressed against each other.

That discrete areas of compression may provide advantages such as, e.g.,improving contact between the device 610 and the thermal block proximateeach of the process chambers. That improved contact may enhance thetransfer of thermal energy into and/or out of the process chambers.Further, the improvements in thermal transmission may be balanced byonly limited thermal transmission into the structure of the carrier 680itself due, at least in part, to the limited contact area between thesample processing device 610 and the carrier 680.

Another potential advantage of selectively compressing discrete areas ofthe device 610 is that weakening of any adhesive bond, delamination ofthe adhesive, and/or liquid leakage from the process chambers 650 may bereduced or prevented by the discrete areas of compression. Thisadvantage may be particularly advantageous when using compressionstructures in the form of collars or other shapes that surround at leasta portion of the process chambers on the sample processing device.

The collars in the depicted embodiment are designed to extend onlypartially about the perimeter of the process chambers 650 and are notdesigned to occlude the feeder conduit entering the process chamber 650.Alternatively, however, collars could be provided that are designed toocclude the feeder conduits, thereby potentially further enhancingisolation between the process chambers during thermal processing ofsample materials.

The collars 684 may optionally provide some reduction in cross-talkbetween process chambers 650 by providing a barrier to the transmissionof electromagnetic energy (e.g., infrared to ultraviolet light) betweenthe process chambers 650 during processing and/or interrogation of theprocess chambers 650. For example, the collars 684 may be opaque toelectromagnetic radiation of selected wavelengths. Alternatively, thecollars 684 may merely inhibit the transmission of electromagneticradiation of selected wavelengths by diffusion and/or absorption. Forexample, the collars 684 may include textured surfaces to enhancescattering, they may include materials incorporated into the body of thecollar 684 and/or provided in a coating thereon that enhance absorptionand/or diffusion.

The carrier 680 may also preferably include force transmissionstructures to enhance the transmission of force from the upper surfaceof the carrier 680 (i.e., the surface facing away from the sampleprocessing device) to the compression structures (in the form of collars684 in the illustrative embodiment) and, ultimately, to the sampleprocessing device itself.

FIG. 19 depicts a portion of one illustrative embodiment of one forcetransmission structure. The force transmission structure is provided inthe form of an arch 685 that includes four openings 682 and is operablyattached to collars 684. The force transmission structure defines alanding area 687 located between the openings 682 and connected to thecollars 684 such that a force 686 applied to the landing area 687 in thedirection of the sample processing device is transmitted to each of thecollars 684, and, thence, to the sample processing device (not shown).In the depicted embodiment, the landing areas are provided by the crownsof the arches 685.

It is preferred that the arch 685 transmit the force evenly between thedifferent collars 684 attached to the arch 685, which are essentiallyprovided as hollow columns supporting the arch 685 (by virtue ofopenings 682). This basic structure is repeated over the entire surfaceof the carrier 680 as seen in, e.g., FIG. 16.

Advantages of providing landing areas on the force transmissionstructures include the corresponding reduction in contact between thecarrier 680 and a platen or other structure used to compress the sampleprocessing device using the carrier 680. That reduced contact canprovide for reduced thermal transmission between the carrier 680 and theplaten or other structure used to compress the sample processing device.In addition, the force transmission structures and correspondingcompression structures on the opposite side of the carrier may allcontribute to reducing the amount of material in the carrier 680,thereby reducing the thermal mass of the carrier 680 (and, in turn, theassembly of carrier 680 and sample processing device).

FIG. 19A illustrates another optional feature of carriers used inconnection with the present invention. The carrier 680′ is depicted withan optical element 688′, e.g., a lens, that may assist in focusingelectromagnetic energy directed into the process chamber 650′ oremanating from the process chamber 650′. The optical element 688′ isdepicted as integral with the carrier 680′, although it should beunderstood that the optical element 688′ may be provided as a separatearticle that is attached to the carrier 680′.

FIG. 19B depicts yet another optional feature of carriers used inconnection with the present invention. The carrier 680″ includes analignment structure 687″ that may be used to assisting guiding a pipette611″ or other sample material delivery device into the appropriateloading structure on the sample processing device 610″. The alignmentstructure 687″ may preferably be removed with the loading structures onthe sample processing device 610″ as described herein. The alignmentstructure 687″ may be generally conical as depicted to guide the pipette611″ if it is slightly off-center from an inlet port into the loadingstructure on sample processing device 610″.

As an alternative the molded carrier depicted in FIGS. 16-19, it may bepossible to use a carrier in the form of a sheet of material in contactwith one side of the sample processing device. FIG. 20 is an explodedview of one illustrative sample processing device 710 and a carrier 780that may be used in connection with the sample processing device 710.

The sample processing device 710 includes a set of process arrays 720,each of which includes process chambers 750 that, in the depicted sampleprocessing device 710, are arranged in an array on the surface of thesample processing device 710. The carrier 780 includes a plurality ofopenings 782 formed therein that preferably align with the processchambers 750 when the sample processing device 710 and carrier 780 arecompressed together.

The carrier 780 may be manufactured of a variety of materials, althoughit may be preferred that the carrier be manufactured of a compressiblematerial, e.g., a sheet of compressible foam or other substance. Inaddition to compressibility, it may be preferred that the compressiblematerial also exhibit low thermal conductivity, low thermal mass, andlow compression set, particularly at the temperatures to which thesample processing device will be subjected. One class of suitable foamsmay include, e.g., silicone based silicone foams.

If the carrier 780 is manufactured of compressible material, there maybe no need to provide relief on the surface of the carrier 780 facingthe sample processing device 710 to prevent premature occlusion of theconduits in the process arrays 720. If, however, the carrier 780 ismanufactured of more rigid materials, it may be desirable to providesome relief in the surface of the carrier 780 for the conduits in theprocess arrays 720.

Similar to the carrier 680 described above, a carrier 780 such as thatdepicted in FIG. 20 may also provide for selective compression of thesample processing devices by not compressing the sample processingdevices in the areas occupied by the process chambers 750 (due to theabsence of material located above the process chambers 750). As aresult, the carrier 780 may also provide advantages in that weakening ofthe adhesive bond, delamination of the adhesive, and/or liquid leakagefrom the process chambers 750 may be reduced or prevented by thecompression provided to the sample processing device 710 outside of theprocess chambers 750. In addition, thermal leakage from, e.g., a thermalblock against which the assembly is urged, may be reduced if thematerial of the carrier 780 has desirable thermal properties (e.g., lowthermal mass, low thermal conductivity, etc.).

The openings 782 may optionally provide some protection reduction incross-talk between process chambers 750 by providing a barrier to thetransmission of electromagnetic energy (e.g., light) between the processchambers 750 during processing and/or interrogation of the processchambers 750. For example, the carrier 780 may be opaque toelectromagnetic radiation of selected wavelengths. Alternatively, thecarrier may merely inhibit the transmission of electromagnetic radiationof selected wavelengths by diffusion and/or absorption. For example, theopenings 782 may include textured surfaces to enhance scattering, thecarrier 780 may include materials incorporated into the body of thecarrier 780 and/or provided in a coating thereon that enhance absorptionand/or diffusion of selected wavelengths of electromagnetic energy.

The carriers described above in connection with FIGS. 16-20 may befixedly attached to the sample processing device or they may be separatefrom the sample processing device. If separate, the carriers may beremovably attached to or brought into contact with each sampleprocessing device in a manner that facilitates removal from an sampleprocessing device without significant destruction of the carrier. As aresult, such carriers may be used with more than one sample processingdevice. Alternatively, however, the carriers may be firmly affixed tothe sample processing device, such that both components are discardedafter use. In some instances, the carrier may be attached to the systemused to process the sample processing devices, e.g., the platen of athermocycling system, such that as an sample processing device is loadedfor thermal processing, the carrier is placed into contact with thesample processing device.

Both of the carriers described above are examples of means forselectively compressing the first side and second side of a sampleprocessing device together about each process chamber. It is preferredthat the compression occur simultaneously about each process chamber.Many other equivalent structures that accomplish the function ofselectively compressing the first side and second side of a sampleprocessing device together about each process chamber may be envisionedby those of skill in the art. In some embodiments, it may be preferredthat the means for selectively compressing applies compressive forceover substantially all of the sample processing device outside of theprocess chambers (e.g., the resilient carrier 780). In otherembodiments, it may be preferred that the means for selectivelycompressing applies compressive forces in only a localized area abouteach of the process chambers in the sample processing device (e.g.,carrier 680 with its associated collars).

Any system incorporating a means for selectively compressing may attachthe means for selectively compressing to the sample processing device orto a platen or other structure that is brought into contact with thesample processing device during processing. FIG. 20A depicts one thermalprocessing system that may be used in connection with the sampleprocessing devices of the present invention in a block diagram format.The system includes an sample processing device 710′ located on athermal block 708′. The temperature of the thermal block 708′ ispreferably controlled by a thermal controller 706′. On the opposite sideof the sample processing device 710′, the means for selectivelycompressing (in the form of carrier 780′) is located between the sampleprocessing device 710′ and a platen 704′. The platen 704′ may bethermally controlled (if desired) by a thermal controller 702′ (thatmay, in some instances, be the same as controller 706′ controlling thetemperature of the thermal block 708′). The sample processing device710′ and the means for selectively compressing 780′ are compressedbetween the platen 704′ and thermal block 708′ as indicated by arrows701′ and 702′ during thermal processing of the sample processing device710′.

FIGS. 21-25 depict various aspects of one apparatus that may be used toisolate the process chambers in a sample processing device of thepresent invention, where that isolation is achieved by occluding themain conduits connecting the loading structures to the process chambers.

FIG. 21 is a schematic diagram of one sealing apparatus 890 that may beused in connection with the sample processing devices of the presentinvention. The sealing apparatus 890 is depicted with a sampleprocessing device 810 loaded within bed 894. The depicted sealingapparatus 890 can be used to seal or occlude the process arrays in asample processing device 810 loaded in bed 894. A device such as sealingapparatus 890 may be particularly useful with sample processing devicesthat include a set of parallel main conduits that can be sealed oroccluded by deforming a portion of the sample processing devices asdiscussed above in various embodiments.

The sealing apparatus 890 includes a base 891 and a bridge 892 that istraversed across a portion of the base 891 in the direction of arrow895. The bridge 892 includes, in the depicted embodiment, a series ofrollers 893 designed to seal or occlude portions of the process arraysby compressing the sample processing device within the bed 894.

The bed 894 may be constructed of a variety of materials, although itmay be preferred that the bed 894 include a layer or layers of aresilient or elastomeric material that provides some support to thesample processing devices and that can also providing somecompressibility in response to the forces generated as the bridge 892 istraversed across the sample processing device 810.

The bed 894 preferably includes a cavity 896 into which the sampleprocessing device 810 is situated such that the upper surface of thesample processing device 810 is generally coplanar with the remainder ofthe bed 894. The cavity 896 may be relatively simple in shape where thesample processing device 810 includes a carrier as described above. Inthose situations, the carrier may preferably include main conduitsupport rails that are located underneath each of the main conduits andsupport the main conduits as the rollers 893 traverse the sampleprocessing device 810. If no carrier is present, or if the carrier useddoes not include support rails for the main conduits, it may be possibleto provide a shaped bed 894 that includes support rails for the portionsof the sample processing device to be compressed by the rollers 893.

Even if a carrier is present as a part of the sample processing device810, portions of the sample processing device 810 may be unsupported bythe carrier, such as the portion including the loading channels (see,e.g., FIG. 17). In those situations, it may be preferred that the bed894 include shaped portions that provide support to the main conduitsoutside of the carrier such that sealing or occlusion of those portionsof the main conduits may be effectively performed using the apparatus890.

Sealing of the main conduits in the sample processing device 810 isaccomplished by traversing the bridge 892 across the sample processingdevice 810 in the direction of arrow 895. As the bridge 892 is moved,the rollers 893 rotated across the surface of the sample processingdevice 810 to effect the sealing of the main conduits in the sampleprocessing device 810. Although the sealing apparatus 890 is depicted asincluding a series of rollers 893, it will be understood that therollers could be replaced by other structural members such as pins,wires, styli, blades, etc., that, rather than rolling across the sampleprocessing device 810, are drawn across the sample processing device 810in a sliding motion. It may, however, be preferred that a rollingstructure be used for sealing the main conduits in sample processingdevice 810 to reduce the amount of friction generated during the sealingprocess.

The rollers 893 (or other sealing structures) may be mounted within thebridge 892 in a variety of manners. For example, the rollers 893 may befixedly mounted within the bridge, such that their height relative tothe base 810 is fixed. Alternatively, one or more of the rollers 893 maybe mounted in a suspension apparatus such that the height of the rollers893 can vary in response to forces generated during sealing. Ifsuspended, the portions of the rollers responsible for sealing each ofthe main conduits in a sample processing device 810 may be individuallysuspended such that each portion of the roller can move independently ofother portions of the roller. As an alternative to individuallysuspended portions of the rollers 893, it may be preferred that eachroller 893 depicted in FIG. 21 be provided as a one-piece cylindricalunit with structures formed on its surface that provide the desiredsealing capabilities.

FIGS. 23 through 25 depict enlarged partial cross-sectional views of thesealing of main conduits using a device such as sealing apparatus 890.As depicted in the series of FIGS. 23-25, it may be preferred that thesealing process be accomplished with a series of rollers (or othersealing structures as discussed above) that occlude the process arrayconduits in a sequential manner. Referring to FIG. 23, for example, theroller 893 a (only a portion of which is depicted in the cross-sectionalview of FIG. 23) may include a ridge 897 a that forces/deforms a portionof the second side 818 of sample processing device 810 into the mainconduit 840. In the depicted view, the main conduit 840 includes samplematerial located therein. Further, the main conduit 840 is supportedagainst the forces applied by the roller 893 by a shaped structureformed in bed 894. If this cross-sectional view were, alternatively,taken along a line running through a carrier, the main conduit may,instead be supported by a main conduit support rail as described abovein connection with the sample processing device/carrier assemblies.

The result of the compression is that a portion of the second side 818and associated adhesive 819 are forced into conduit 840 (towards thefirst side 816) of the sample processing device 810. The deformation ofthe second side 818 may preferably result in occlusion of the mainconduit that is partial. The partial occlusion may preferably beaccompanied by adhesion of the first side 816 to the second side 818using adhesive 819 within the main conduit 840. In some instances, thispartial occlusion of the main conduit 840 may be sufficient to isolatethe various process chambers located along the main conduit 840. As aresult, the view depicted in FIG. 23 may be one of a sealed processedarray in some instances.

It may, however, be preferred that the main conduit 840 be more occludedthan that depicted in FIG. 23. FIG. 24 depicts a second roller 893 b andassociated ridge 897 b That presents a more rounded profile than theprofile of ridge 897 a depicted in FIG. 23. The more rounded profile ofridge 897 b may be shaped to have a more complementary fit with the mainconduit 840 of sample processing device 810. As a result of that morecomplementary shape, the ridge 897 b may preferably cause substantiallycomplete occlusion of the main conduit 840, thereby adhering the firstside 816 together with the second side 818 within the main conduit 840.

Where the second side 818 is deformed to occlude the main conduit 840and the sample processing device is constructed using an adhesivebetween the first side 816 and the second side 818, deformation of thesample processing device 810 may result in some delamination between thefirst side 816 and the second side 818, particularly along the edges 898of the main conduit 840 as depicted in FIG. 24. Thus, in some instances,it may be desirable to perform a secondary relamination operation afteroccluding the main conduits.

FIG. 25 depicts one mechanism that may be used to address thedelamination in the form of a roller 893 c that is designed to compressthe first side 816, second side 818, and adhesive 819 against the bed894 to relaminate the sample processing device along the edges 898 ofthe main conduit 840.

The rollers or other sealing structures, e.g., pins, blades, etc., maybe manufactured of a variety of materials depending on the constructionof the sample processing devices to be sealed. The sealing structuresmay, for example, be constructed of elastomeric coated rollers or otherstructures, they may be coated with low surface energy materials toreduce friction, they may be constructed entirely of rigid materials(e.g., metals, rigid polymers, etc.). Further, where multiple sealingstructures are used (such as the three rollers 893 depicted in FIG. 21),the different sealing structures may be constructed of a variety ofmaterials, some rigid, some resilient, some including rigid andresilient portions. For example, the roller 893 b may preferably beconstructed of rigid base roll with only the ridge 897 b constructed ofresilient material to better conform to the shape of the main conduit840. Alternatively, the base roll may be resilient while the ridge 897 bis constructed of rigid materials.

Some Alternative Constructions

FIGS. 26A-26F depict some additional optional features that may beincluded as a part of the deformable seal used to close the mainconduits and/or the feeder conduits (if any) in sample processingdevices of the present invention. One optional feature includes a sealstructure 935 and a conformable seal element 936 located in area 934 ofconduit 932. It will be understood that although both features areillustrated together in FIGS. 3A and 3B, either one may be providedalone to enhance closure of the conduit 932 in area 934.

The seal structure 935 may be provided as illustrated, where it isintegral with the first side 950. Alternatively, it could be provided asan additional element attached to the substrate 152 or the adhesive 154after it is attached to the substrate 152. Regardless of its exactconstruction, it is preferred that the seal structure extend into theconduit 932 to provide a structure against which the second side 960 canbe pressed to seal the distribution channel 932. By providing adiscontinuity in the otherwise preferably uniform cross-section of theconduit 932, the seal structure 935 may enhance occlusion of the conduit932. Furthermore, although only one seal structure 935 is illustrated,multiple seal structures may be provided, e.g., in the form of alignedridges. It may be preferred that the seal structure extend across thefull width of the conduit 932 Additionally, the seal structure may takea variety of shapes, with the illustrated rounded ridge being only oneexample. Other potential shapes may include, but are not limited to,rectangular ridges, triangular ridges, etc.

Like the seal structure 935, the conformable seal element 936 may beprovided to enhance occlusion of the conduit 932 in the area 934 andpreferably exhibits some conformance in response to the compressiveforces used to occlude the conduit 932. That conformability may improveclosure of the conduit 932 after the deformation force is removed. Whenused with a seal structure 935 that provides a discontinuity on theopposing surface of the conduit 932, the conformable seal element 936may be even more effective at closing the conduit 932 as it conforms tothe seal structure 935 (see FIG. 26B).

The conformable seal element 936 may be provided in a variety of forms.For example, the conformable seal element 936 may be provided as adiscrete structure, e.g., an elastomer such as silicone, a conformablepressure sensitive adhesive, a wax, etc. Alternatively, the conformableseal element 936 may be provided within the various sub-layers formingthe side 960 of the device 910. In yet another alternative, theconformable seal element 936 may be provided as a thickened area of theone of the layers within the side 960, e.g., layer 962, 964, or 966.

FIGS. 26C and 26D illustrate an alternative area 934′ of conduit 932′that includes other optional features used to close conduit 932′ influid communication with process chamber 920′. The area 934′ includescomplementary mating seal structures 937′ and 938′ formed on theopposing sides 950′ and 960′ of the conduit 932′. When deformed duringclosure of the conduit 932′, the mating structures 937′ and 938′ mayprovide a more tortuous fluid path, thereby improving closure of theconduit 932′.

In yet another alternative, the seal structure 938′ provided on thesecond side 960′ may be provided alone, with the adhesive 954′ being ofa uniform thickness. The adhesive 954′ may, however, exhibit somedeformation as a result of the compressive force used to close theconduit 932′ and that deformation may improve occlusion of the conduit932′. In addition, the adhesive 954′ may preferably adhere to the sealstructure 938′, thereby further improving closure of the conduit 932′.

Yet another illustrative structure that may enhance occlusion of theconduit 932″ is depicted area 934″ in FIGS. 26E and 26F. The structurein area 934″ includes a cavity 939″ formed in the first side 950″ of thedevice. The cavity 939″ may preferably include a conformable sealelement 936″ that is forced against the opposing side of the conduit932″ when the cavity 939″ is depressed. The conformable seal element936″ may be, e.g., an elastomer, a pressure sensitive adhesive, a wax,etc. The cavity 939″ may preferably be dome-shaped such that pressurecauses it to extend into the conduit 932″ as illustrated in FIG. 26F.

One potential advantage of the structures in area 934″ is that, beforeclosure, no portion of the structures in area 934″ extends into theconduit 932″ to impede or disrupt flow therethrough. Another potentialadvantage of the structures illustrated in FIGS. 26E and 26F is thatregistration of the two sides 950″ and 960″ may not be required duringbonding of the two major sides because the structures are all located onone side of the device.

As an alternative to the structure shown in FIGS. 26E and 26F, theconformable seal element may be provided as a layer of pressuresensitive adhesive on the second major side 960″ against which thecavity 939″ is forced upon closure of the conduit 932″.

FIGS. 27A & 27B depict yet another potential variation for thedeformable seals that may be used to isolate process chambers in sampleprocessing devices of the present invention. The depicted seal structure1070 may be located along a conduit 1060 (e.g., main conduit or feederconduit). The seal structure 1070 may be provided in the form ofmaterial located along the conduit 1060. When heated above a selectedtemperature, the material of the seal structure 1070 deforms (in theillustrated case the deformation is in the form of expansion) topartially or completely occlude the conduit 1060. The material used inthe seal structure 1070 may be, e.g., polymer that expands to form afoamed polymer. The foaming action may be provided, e.g., by using ablowing agent or supercritical carbon dioxide impregnation.

Where a blowing agent is used in the seal structure 1070, it may beimpregnated into the polymer. Examples of suitable blowing agentsinclude, but are not limited to: CELOGEN AZ (available from UniroyalCorporation, Middlebury, Conn.), EXPANCEL microspheres (Expancel,Sweden), and glycidyl azide based polymers (available from MinnesotaMining and Manufacturing Company, St. Paul, Minn.). When the impregnatedpolymer is then heated above a selected temperature, the blowing agentgenerates a gas that causes the polymer to foam and expand and close theseal structure 1070 as depicted in FIG. 27B.

Supercritical foaming may also be used to occlude the conduit 1060 byexpanding the seal structure 1070. A polymer may be caused to foam byimpregnating the polymer with, e.g., carbon dioxide, when the polymer isheated above its glass transition temperature, with the impregnatingoccurring under high pressure. The carbon dioxide may be applied inliquid form to impregnate the polymeric matrix. The impregnated materialcan be fabricated into the valve structure, preferably in a compressedform. When heated the carbon dioxide expands, the structure also deformsby expanding, thereby closing the conduit 1060.

FIGS. 28A and 28B depict one alternative construction for a sampleprocessing device 1110 according to the present invention. The sampleprocessing device 1110 includes a core 1190, a first side 1150 attachedto one major surface of the core 1190 and a second side 1160 attached tothe other major surface of the core 1190. The second side 1160preferably includes a metallic layer 1162 and passivation layer 1164that is located between the metallic layer 1162 and the core 1190.

The core 1190 includes a plurality of voids 1122 formed therein thatextend through both major surfaces of the core 1190. The voids 1122,together with the first and second sides 1150 and 1160 define processchambers 1120 of the sample processing device 1110. In addition to thevoids 1122, the process chamber volume may further be defined bystructures formed in one or both of the sides. For example, the secondside 1160 includes structures in the form of depressions that increasethe volume of the process chambers 1120.

The core 1190 may also include elongated voids 1134 that form conduits1132 in fluid communication with the process chambers 1120. The voids1134 may be formed completely through the core 1190 as are the voids1122 forming the process chambers 1120 or they may be formed onlypartially through the thickness of the core 1190.

The core 1190 may be formed of a variety of materials, although it maybe preferable to manufacture the core 1190 from polymeric materials.Examples of suitable polymeric materials include, but are not limitedto, polypropylene, polyester, polycarbonate, polyethylene, etc. It mayfurther be preferred that the core 1190 be manufactured of materialsthat are compatible with the reactions and any materials (samples,reagents, etc.) that may be located within the process chambers 1120.

The second side 1160 may be manufactured of materials similar to thoseused in, e.g., the construction of the sample processing devicesdescribed above. The adhesive layers 1154 and 1164 used to connect thesides 1150 and 1160 to the core 1190 may be the same or different. As analternative to the adhesives, the layers 1154 and/or 1164, or theirrespective substrates 1152 and/or 1162, may be constructed of materialsthat are amenable to melt bonding to the core 1190.

Patents, patent applications, and publications disclosed herein arehereby incorporated by reference as if individually incorporated. It isto be understood that the above description is intended to beillustrative, and not restrictive. Various modifications and alterationsof this invention will become apparent to those skilled in the art fromthe foregoing description without departing from the scope of thisinvention, and it should be understood that this invention is not to beunduly limited to the illustrative embodiments set forth herein.

1. A method of closing deformable seals in a sample processing device,the method comprising: providing a sample processing device comprising abody that comprises a first side attached to a second side, and one ormore process arrays formed between the first and second sides, whereineach process array of the one or more process arrays comprises a loadingstructure, a main conduit comprising a length, a plurality of processchambers distributed along the main conduit, wherein the loadingstructure is in fluid communication with the plurality of processchambers through the main conduit, and a deformable seal located alongthe main conduit between the loading structure and the plurality ofprocess chambers; locating the sample processing device in a sealingapparatus, the sealing apparatus comprising a base adapted to retain thesample processing device; a bridge operatively attached to the base, thebridge mounted for movement across the base; and one or more sealingstructures attached to the bridge, the one or more sealing structuresfacing the sample processing device in the base; and closing at least aportion of the deformable seals in the sample processing device locatedon the base by traversing the base with the bridge while the sampleprocessing device is located between the base and the bridge, whereinthe one or more sealing structures deform at least a portion of thesecond side of the body to close the deformable seals.
 2. The method ofclaim 1, wherein closing at least a portion of the deformable sealscomprises sliding the one or more sealing structures across the sampleprocessing device.
 3. The method of claim 2, wherein the one or moresealing structures are selected from the group consisting of a pin, astylus, a blade, and a wire.
 4. The method of claim 2, wherein the oneor more sealing structures comprise low surface energy materials toreduce friction during the sliding.
 5. The method of claim 1, whereinclosing at least a portion of the deformable seals comprises rolling theone or more sealing structures across the sample processing device. 6.The method of claim 5, wherein the one or more sealing structurescomprise a roller that comprises a plurality of ridges, wherein eachridge of the plurality of ridges is adapted to deform at least a portionof the deformable seal as the bridge traverses the base.
 7. The methodof claim 1, wherein each sealing structure of the one or more sealingstructures is fixedly mounted within the bridge such that the height ofthe sealing structure relative to the base is fixed.
 8. The method ofclaim 1, wherein each sealing structure of the one or more sealingstructures is individually suspended in the bridge such that the heightof the sealing structure can vary in response to forces generated as thebridge traverses the base.
 9. The method of claim 1, wherein the basecomprises a cavity, wherein locating the sample processing device in thesealing apparatus comprises locating the sample processing device in thecavity.
 10. The method of claim 1, wherein the deformable seal in eachprocess array of the plurality of process arrays comprises a deformablemetallic layer forming a portion of the second side of the body, whereinthe one or more sealing structures deform at least a portion of themetallic layer to close the deformable seal.
 11. The method of claim 1,wherein the deformable seal in each process array of the plurality ofprocess arrays comprises pressure sensitive adhesive located between thefirst side and the second side of the body, wherein closing thedeformable seal comprises adhering the first side and the second sidetogether using the pressure sensitive adhesive.
 12. The method of claim1, wherein the deformable seal in each process array of the plurality ofprocess arrays comprises a deformable metallic layer forming a portionof the second side of the body and pressure sensitive adhesive locatedbetween the first side and the second side of the body, wherein closingthe deformable seal in each process array of the plurality of processarrays comprises deforming at least a portion of the metallic layer andadhering the first side and the second side together using the pressuresensitive adhesive.
 13. The method of claim 1, wherein the sampleprocessing device comprises a plurality of process arrays, wherein eachprocess array of the plurality of process arrays comprises a deformableseal, and wherein closing at least a portion of the deformable seals inthe sample processing device comprises simultaneously closing thedeformable seals in the plurality of process arrays.
 14. A sealingapparatus for closing deformable seals in a sample processing devicethat includes a body with a deformable seal located therein, theapparatus comprising: a base adapted to retain a sample processingdevice; a bridge operatively attached to the base, the bridge mountedfor traversing movement across the base; and one or more sealingstructures attached to the bridge, the sealing structures facing thebase, wherein each sealing structure of the one or more sealingstructures is adapted to deform at least a portion of a deformable sealin a sample processing device located on the base as the bridgetraverses the base.
 15. The sealing apparatus of claim 14, wherein eachsealing structure of the one or more sealing structures is a slidingstructure.
 16. The sealing apparatus of claim 15, wherein the slidingstructure is selected from the group consisting of a pin, a stylus, ablade, and a wire.
 17. The sealing apparatus of claim 15, wherein thesliding structure comprises low surface energy materials to reducefriction during sliding.
 18. The sealing apparatus of claim 14, whereineach sealing structure of the one or more sealing structures comprises aroller that rotates as the bridge is moved across the base.
 19. Thesealing apparatus of claim 14, wherein the roller comprises a pluralityof ridges, wherein each ridge of the plurality of ridges is adapted todeform at least a portion of a deformable seal in a sample processingdevice located on the base as the bridge traverses the base.
 20. Thesealing apparatus of claim 14, wherein each sealing structure of the oneor more sealing structures is fixedly mounted within the bridge suchthat the height of the sealing structure relative to the base is fixed.21. The sealing apparatus of claim 14, wherein each sealing structure ofthe one or more sealing structures is individually suspended in thebridge such that the height of the sealing structure can vary inresponse to forces generated as the bridge traverses the base.
 22. Thesealing apparatus of claim 14, wherein the base comprises a cavityadapted to receive the sample processing device.
 23. The sealingapparatus of claim 14, wherein the one or more sealing structures followparallel paths across the base as the bridge traverses the base.
 24. Thesealing apparatus of claim 14, wherein two or more sealing structures ofthe one or more sealing structures are arranged to pass sequentiallyover the base, wherein each sealing structure of the two or more sealingstructures is adapted to sequentially compress the same deformable sealin the sample processing device as the bridge traverses the base. 25.The sealing apparatus of claim 24, wherein the two or more sealingstructures comprise the same profile.
 26. The sealing apparatus of claim24, wherein the two or more sealing structures comprise differentprofiles.